The sodium current (I-Na) plays a key role in cardiac excitation. This project proposes to investigate the normal and abnormal physiology of I-Na in canine cardiac Purkinje cells. Most present knowledge of I-Na comes from work done on squid axon and other nerve tissue, because technical limitations have limited direct investigation of I-Na in cardiac tissue. The behavior of I-Na in cardiac tissue differs from that in nerve, so to simply extrapolate studies in nerve is unwise and may lead to incorrect conclusions. The techniques of voltage clamp and internal perfusion of single cardiac cells allow for control of the cell's biochemical and electrical environment, making possible the investigation of cardiac I-Na and its pathophysiology in ischemia. This study proposes to do the following: 1) Systematically study the voltage and time dependent kinetics of I-Na in cardiac Purkinje cells and determine the mechanisms by which different internal and external ion substitutions affect these kinetics. 2) Simulate conditions found in ischemia to determine if changes in intrinsic I-Na channel properties contribute to the changes in I-Na observed during ischemia. 3) Describe the kinetics of I-Na under the various conditions studied by means of mathematical models. Better understanding of cardiac I-Na and its derangements should lead to better understanding and treatment of cardiac arrhythmia.